The proposed research is aimed at elucidation of relationships which may exist between variations in plasma membrane calcium transport and the expression of certain human diseases. The red blood cell will be used. Major emphasis will be on clarification of the regulation of calcium transport in normal human cells and possible variation(s) sickle cell anemia, cystic fibrosis, and muscular dystrophy. The calcium pump is based on a membrane-bound (Ca2 ion plus Mg2 ion)-ATPase. Calmodulin, which is a protein present in red blood cells, increases the activity of the calcium pump ATPase. The hypothesis to be tested is that the calmodulin acts as a switch which turns on the plasma membrane calcium pump. It is anticipated that results of the proposed research will provide further information on the plasma membrane calcium transport system in normal cells and variations which exist in certain diseases.